Characterization and genome analysis of novel bacteriophages infecting the opportunistic human pathogens Klebsiella oxytoca and K. pneumoniae

Park, Eun‐Ah; Kim, You‐Tae; Cho, Jaehyun; Ryu, Sangryeol; Lee, Ju-Hoon

doi:10.1007/s00705-016-3202-3

Cited by 19 publications

(9 citation statements)

References 36 publications

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“…Interestingly, in the temperature range from −20 and 70 • C, it was observed that ZCKP8 was relatively thermally stable. ZCKP8 maximal activity was detected at 50 • C, with a moderate decrease of 2 log 10 PFU/mL at 70 • C. K. pneumoniae phages, including wKp-lyy15, phage Z, PKP126, vB_Klp_1, vB_Klp_3, vB_Klp_4, vB_Klp_5, and vB_Klp_6, were previously mentioned to be active at 70 • C [29][30][31].…”

Section: Discussionmentioning

confidence: 84%

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Topically Applied Bacteriophage to Control Multi-Drug Resistant Klebsiella pneumoniae Infected Wound in a Rat Model

et al. 2021

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(Background): Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) has steadily grown beyond antibiotic control. Wound infection kills many patients each year, due to the entry of multi-drug resistant (MDR) bacterial pathogens into the skin gaps. However, a bacteriophage (phage) is considered to be a potential antibiotic alternative for treating bacterial infections. This research aims at isolating and characterizing a specific phage and evaluate its topical activity against MDR-KP isolated from infected wounds. (Methods): A lytic phage ZCKP8 was isolated by using a clinical isolate KP/15 as a host strain then characterized. Additionally, phage was assessed for its in vitro host range, temperature, ultraviolet (UV), and pH sensitivity. The therapeutic efficiency of phage suspension and a phage-impeded gel vehicle were assessed in vivo against a K. pneumoniae infected wound on a rat model. (Result): The phage produced a clear plaque and was classified as Siphoviridae. The phage inhibited KP/15 growth in vitro in a dose-dependent pattern and it was found to resist high temperature (˂70 °C) and was primarily active at pH 5; moreover, it showed UV stability for 45 min. Phage-treated K. pneumoniae inoculated wounds showed the highest healing efficiency by lowering the infection. The quality of the regenerated skin was evidenced via histological examination compared to the untreated control group. (Conclusions): This research represents the evidence of effective phage therapy against MDR-KP.

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Section: Discussionmentioning

confidence: 84%

“…ZCKP8 maximal activity was detected at 50 °C, with a moderate decrease of 2 log 10 PFU/mL at 70 °C. K. pneumoniae phages, including wKp-lyy15, phage Z, PKP126, vB_Klp_1, vB_Klp_3, vB_Klp_4, vB_Klp_5, and vB_Klp_6, were previously mentioned to be active at 70 °C [ 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Topically Applied Bacteriophage to Control Multi-Drug Resistant Klebsiella pneumoniae Infected Wound in a Rat Model

et al. 2021

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“…Of those which are reported as targeting K . oxytoca , most belong to the Myoviridae family, with genomes ranging in size from 168 to 174 Kb [ 30 , 31 , 43 ]. KOX1, the unique K .…”

Section: Discussionmentioning

confidence: 99%

“…pneumoniae were able to lyse strains of K . oxytoca [ 30 , 31 , 43 ], KOX1 was specific for K . oxytoca bacteria, and did not readily lyse the K .…”

Section: Discussionmentioning

confidence: 99%

Characterization and formulation into solid dosage forms of a novel bacteriophage lytic against Klebsiella oxytoca

et al. 2017

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AimTo isolate and characterize bacteriophage lytic for the opportunistic pathogen Klebsiella oxytoca and their formulation into a range of solid dosage forms for in-vitro testing.Methods and resultsWe report the isolation, genomic and functional characterization of a novel bacteriophage lytic for Klebsiella oxytoca, which does not infect the closely related Klebsiella pneumoniae. This bacteriophage was formulated into suppositories and troches and shown to be released and lyse underlying Klebsiella oxytoca bacteria in an in-vitro model. These bacteriophage formulations were stable for at least 49 days at 4°C.ConclusionsThe successful in-vitro assay of these formulations here suggests that they could potentially be tested in-vivo to determine whether such a therapeutic approach could modulate the gut microbiome, and control Klebsiella oxytoca overgrowth, during antibiotic therapy regimes.Significance and impact of the studyThis study reports a novel bacteriophage specific for Klebsiella oxytoca which can be formulated into solid dosage forms appropriate for potential delivery in testing as a therapy to modulate gut microbiome during antibiotic therapies.

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“…Stability of the phages to temperature and pH was assessed by phage titration after incubation in SM buffer at different temperature or pH values (Park et al, 2017). Briefly, 1.5 mL tubes containing the same amount of the purified phages…”

Section: Thermal and Ph Stabilitymentioning

confidence: 99%

The Novel Enterococcus Phage vB_EfaS_HEf13 Has Broad Lytic Activity Against Clinical Isolates of Enterococcus faecalis

Lee

et al. 2019

Front. Microbiol.

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Enterococcus faecalis is a Gram-positive, facultative anaerobic bacterium frequently found in the gastrointestinal tract, oral cavity, and periodontal tissue. Although it is considered a commensal, it can cause bacteremia, endocarditis, endodontic infections, and urinary tract infections. Because antibiotics are cytotoxic not only to pathogens, but also to health-beneficial commensals, phage therapy has emerged as an alternative strategy to specifically control pathogenic bacteria with minimal damage to the normal flora. In this study, we isolated a novel phage, Enterococcus phage vB_EfaS_HEf13 (phage HEf13), with broad lytic activity against 12 strains of E. faecalis among the three laboratory strains and 14 clinical isolates of E. faecalis evaluated. Transmission electron microscopy showed that phage HEf13 has morphological characteristics of the family Siphoviridae. Phage HEf13 was stable at a wide range of temperature (4-60 • C) and showed tolerance to acid or alkaline (pH 3-12) growth conditions. Phage HEf13 had a short latent period (25 min) with a large burst size (approximately 352 virions per infected cell). The lytic activity of phage HEf13 at various multiplicities of infection consistently inhibited the growth of diverse clinical isolates of E. faecalis without any lysogenic process. Moreover, phage HEf13 showed an effective lytic activity against E. faecalis on human dentin ex vivo infection model. Whole genome analysis demonstrated that the phage HEf13 genome contains 57,811 bp of double-stranded DNA with a GC content of 40.1% and 95 predicted open reading frames (ORFs). Annotated functional ORFs were mainly classified into four groups: DNA replication/packaging/regulation, phage structure, host cell lysis, and additional functions such as RNA transcription. Comparative genomic analysis demonstrated that phage HEf13 is a novel phage that belongs to the Sap6virus lineage. Furthermore, the results of multiple sequence alignment showed that polymorphism of phage infection protein of E. faecalis (PIP EF) contributes to determine the host specificity of phage HEf13 against various E. faecalis strains. Collectively, these results suggest that phage HEf13 has characteristics of a lytic phage, and is a potential therapeutic agent for treatment or prevention of E. faecalis-associated infectious diseases.

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Characterization and genome analysis of novel bacteriophages infecting the opportunistic human pathogens Klebsiella oxytoca and K. pneumoniae

Cited by 19 publications

References 36 publications

Topically Applied Bacteriophage to Control Multi-Drug Resistant Klebsiella pneumoniae Infected Wound in a Rat Model

Topically Applied Bacteriophage to Control Multi-Drug Resistant Klebsiella pneumoniae Infected Wound in a Rat Model

Characterization and formulation into solid dosage forms of a novel bacteriophage lytic against Klebsiella oxytoca

The Novel Enterococcus Phage vB_EfaS_HEf13 Has Broad Lytic Activity Against Clinical Isolates of Enterococcus faecalis

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